This proposal seeks to continue and to expand the Laboratory of Applied Pharmacokinetics at the University of Southern California School of Medicine, to increase mathematical expertise in describing clinically important events and problems, and to use this expertise to increase our ability to predict and thus to control clinical behavior. In this effort, stacked multi-compartment models of drugs and metabolites will be employed, and multiple adaptive algorithms and parameter adjustments will be used. Simultaneous achievement of multiple therapeutic goals will be sought. Computations of "conditional anticipated risk" will be developed. Furthermore, this project will also seek to depart, from a strict multi-compartment analysis, when needed, to a more subtle and flexible analysis of the raw behavioral relationships between the patient's clinical state, the drug therapy given, and his resultant change in clinical behavior, using "input-output" techniques. This new mathematical expertise, some of which will involve new research in fundamental mathematics, will be applied to projects of digitalis therapy and the therapy of arrhythmias with procainamide and lidocaine. Lidocaine therapy of suspected myocardial infarction by paramedics in ambulances will also be studied. Antibiotic therapy of newborns and adults will also be studied, as will "input-output" descriptions of the clinical and therapeutic situations relating to diabetic acidosis and to anticoagulant therapy with heparin. As these improved capabilities become available, they will be cast in the form of interactive time-shared computer programs and added to the current USC PACK collection, the internationally accessed package of time-shared computer programs in routine daily use for drug dosage regimens in community hospitals.